Antibacterial activity of BMY-28142, a novel broad-spectrum cephalosporin

BMY-28142, 7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3- (1-methylpyrrolidinio)methyl-3-cephem-4-carboxylate, exhibited a well-balanced, extended-spectrum of antibacterial activity both in vitro and in vivo. Against Staphylococci and Streptococci, BMY-28142 was about four to ten times more active than ceftazidime and comparable to cefotaxime. Most Enterobacteriaceae were more susceptible to BMY-28142 than to ceftazidime, though strains of Pseudomonas aeruginosa were slightly more sensitive to ceftazidime. BMY-28142 showed potent activity against Gram-negative bacteria resistant to ceftazidime and/or cefotaxime. Bactericidal activity of BMY-28142 against 10 strains of P. aeruginosa was superior to that of ceftazidime. In bacterial infection models in mice, BMY-28142 was more effective than ceftazidime against three Gram-positive and three Gram-negative pathogens. The anti-pseudomonal in vivo activity of BMY-28142 was nearly comparable to that of ceftazidime. The blood levels and urinary excretion rates of BMY-28142 in mice were similar to those of ceftazidime.